Insight 1

•  Chronic inflammation could be a potential link between MetS and Major Depressive Disorder (MDD). The conditions that comprise MetS (i.e obesity, hypertension) have been found to have a low-grade, chronic inflammatory component created through the release of pro-inflammatory cytokines due to cardiovascular damage. In MDD pro-inflammatory cytokines play a role in disrupting neurotransmitter synthesis and signal transduction. From the literature, a connection could be made that in the presence of MetS, pro-inflammatory cytokines lead to alteration of neurotransmitter synthesis and regulation which could lead to MDD.

Insight 2

• Antidepressant use amongst those who have clinically diagnosed depression was associated with a higher prevalence of MetS and could exacerbate MetS symptoms. Multiple antidepressants are marketed and each influences metabolic factors differently but studies have found that antidepressant use in individuals both diagnosed and undiagnosed with MetS was associated with a higher prevalence of biomarkers associated with MetS. One study specifically cited higher elevated fasting glucose, hypertension, and low HDL-cholesterol, which are all links to MetS development. One caveat is that not all antidepressants change the same parameters. For example, selective serotonin reuptake inhibitors (SSRIs) appear to elevate C-reactive protein, a biomarker of MetS, but may not necessarily elevate lipids, especially when given with Tricyclic antidepressants (TCA). Despite this, the literature appears to point to antidepressants as having a negative impact on the MetS development or exacerbation. This means that another connection between depression and MetS could be through treatment for depression as well as inflammatory mechanisms.

Insight 3

• The relationship between psychological stressors and MetS appears to be a bidirectional interaction. The literature shows that individuals who suffer from MDD have increased activation of the immune system and thus pro-inflammatory cytokines which could lead or exacerbate MetS. As aforementioned, MetS also has a pro-inflammatory component. This has been illustrated in studies that show that individuals with MetS have a higher prevalence of depression than those without and that those with depression have a higher prevalence of MetS. The temporal relationship (which one comes first) has yet to be found but the relationship appears to be reciprocal in that each exacerbates the development of the other and individuals may have underlying predispositions for both disorders. The exact mechanism of the reciprocity has yet to be elucidated but some suggestions have also been shown in components of MetS such as depression and diabetes or depression and obesity.

Insight 4

•  Anxiety has been found to be strongly associated with MetS development. The exact pathophysiology or type of relationship has yet to be fully elucidated but it is proposed that anxiety could precede MetS development. Anxiety activates the sympathetic nervous system and influences many bodily organs particularly the heart. These events, if chronic, could lead to poor cardiovascular health such as hypertension. Another possibility could be through hypothalamic-pituitary-adrenocortical dysregulation which would lead to elevated cortisol which could also lead to poor metabolic outcomes. A final suggestion is that inflammation could also underlay chronic anxiety which, as has been discussed, could also lead to MetS development.

Insight 5

•  One study found that parental depression was associated with a negative effect on adolescents (age 11-18) and could lead to the development of MetS later in life. According to the study, adolescents developed poor self-regulation skills including poor health behaviors in connection with parental depression. The reasoning behind the finding was that parental depression created stress within the child's life especially when factoring in potential deficits in child-rearing. The parental depression could also put the child at risk for developing depression or anxiety later in life thus potentially creating the bidirectional relationship between psychological stressors and MetS. By age 25 adolescents had either diagnosed MetS or symptoms predisposing to MetS. This study provides another factor in that MetS development could be due to childhood environmental stressors influenced by parental behaviors.